Viruses are significant causes of human birth defects. Recent animal experiments show that viruses can produce fetal defects similar to many in man of unknown cause. Studies here have produced multiple malformations in fetal swine infected with Hog Cholera virus. The malformed organs contain no histologic evidence of infection, even though the fetuses remain persistently infected and seem immunologically tolerant to the agent. These experiments will be expanded to (1) note the effects on the fetus when the infection is initiated at different stages of pregnancy, (2) determine the mechanism of CNS malformation and hypomyelinogenesis, and (3) investigate the apparent lack of a fetal immune response. Cytomegaloviruses (CMV) are the most common viral pathogens known to affect the human fetus. Similar CMV infections in pregnant guinea pigs might elucidate the pathogenesis of the human infection. Pregnant guinea pigs inoculated at various periods of gestation will be sacrificed and the fetuses assayed by virological, immunofluorescent, histological, and serological methods, hoping to define and then explore a model disease similar to human gestational CMV infections. In addition, fresh nervous system tissues obtained at autopsy from abnormal human fetuses and stillborn infants will be examined with histological, tissue culture and immunofluorescent techniques. Such studies will hopefully uncover active, latent or non-cytolytic human viral teratogens with characteristics similar to those recently defined in experimental animals.